Single drug injection wards off COVID-19 hospitalizations

A single injection of PEG-lambda interferon proved to be effective against all variants of the coronavirus tested by researchers at Stanford Medicine.
Image Credit: Gerd Altmann

In an international, multicenter, pivotal Phase 3 trial, a single under-the-skin injection of a biological drug given to patients within seven days of the onset of COVID-19 symptoms cut the likelihood they needed to be hospitalized in half. Patients treated within three days of showing symptoms fared even better. Among unvaccinated patients who were treated soon after symptom onset, hospitalization likelihood plummeted markedly.

The drug, pegylated lambda-interferon, or PEG-lambda, proved effective against all COVID-19 viral variants tested, including omicron. Side effects were no greater than those reported by placebo recipients.

A report on the success of the randomized, double-blind, placebo-controlled trial of nearly 2,000 newly infected COVID-19 patients was published online Feb. 9 in the New England Journal of Medicine.

PEG-lambda is a synthetic version of lambda-interferon, a naturally occurring protein that infected cells secrete as a first line of defense against viral infection.

Deep-sea black carbon comes from hydrothermal vents

Research Vessel Hakuho Maru conducted the observations used for this study.
Photo Credit: Courtesy of Hokkaido University

Hydrothermal vents have been identified as a previously undiscovered source of dissolved black carbon in the oceans, furthering the understanding of the role of oceans as a carbon sink.

The ocean is one of the largest dynamic carbon sinks in the world, and is susceptible to increased carbon emissions from human activities. There are even proposals to use the ocean to sequester carbon in an effort to reduce carbon emissions. However, much of the processes by which the ocean functions as a carbon sink are not fully understood.

Associate Professor Youhei Yamashita and grad student Yutaro Mori at Hokkaido University, along with Professor Hiroshi Ogawa at AORI, The University of Tokyo, have revealed conclusive evidence that hydrothermal vents are a previously unknown source of dissolved black carbon in the deep ocean. Their discoveries were published in the journal Science Advances.

“One of the largest carbon pools on the Earth’s surface is the dissolved organic carbon in the ocean,” explains Ogawa. “We were interested in a portion of this pool, known as dissolved black carbon (DBC), which cannot be utilized by organisms. The source of DBC in the deep sea was unknown, although hydrothermal vents were suspected to be involved.”

NIH scientists discover a rare neurological disease involving cellular recycling

Image Credit: Raman Oza

A new disease could provide insights into how the cell’s recycling system contributes to a healthy brain.

Researchers at the National Institutes of Health have discovered a new neurological condition characterized by issues with motor coordination and speech. They report their findings in npj Genomic Medicine.

Scientists from NIH’s National Human Genome Research Institute (NHGRI) and Undiagnosed Diseases Program (UDP) identified three children with the condition, two siblings and an unrelated child. The three children all had issues with motor coordination and speech, and one child had abnormalities in the cerebellum, the part of the brain involved in complex movement among other functions. Additionally, the children all had mutations in both copies of the ATG4D gene.

ATG4D aids in the cellular housekeeping process called autophagy, which cells use to break down and recycle damaged proteins and other defective pieces of the cell to stay healthy. Autophagy is a fundamental process used by cells throughout the body, but neurons are particularly dependent on autophagy for survival. However, little is known about how ATG4D contributes to healthy neurons.

The first inclination of ATG4D’s effects on brain health came from a 2015 study in which researchers identified a genetic neurological disease among Lagotto Romagnolo dogs, an Italian breed known for their fluffy coats and truffle-hunting abilities. The affected dogs had abnormal behavior, atrophy of the cerebellum, issues with motor coordination and eye movement and ATG4D mutations.

DNA stuck in the gears of the RNA production machine

Researchers have worked out the mechanism of transcription pausing in some bacteria by determining the structures of RNA polymerase in a complex with a DNA template, an RNA product, and a protein factor using cryo-electron microscopy (cryo-EM). The nucleotide addition cycle of bacterial RNA polymerase (RNAP) is depicted by cartoon models of template DNA (tDNA, green), RNA (red), trigger loop (TL, magenta), bridge helix (BH, blue), incoming NTP (red) and Mg2+ (yellow spheres) together with the conformational changes of RNAP (swiveling, folding Trigger loop) associated with each step of the nucleotide addition cycle. NusG and non-template DNA (ntDNA, light green) interaction (center panel) inhibits the RNAP swiveling, the Trigger loop folding allosterically thus pauses RNA synthesis.
Illustration Credit: Murakami Laboratory / Pennsylvania State University

Precise control of gene expression — ensuring that cells make the correct components in the right amount and at the right time — is vital for all organisms to function properly. Cells must regulate how genes encoded in the sequence of DNA are made into RNA molecules that can carry out cellular functions on their own or be further processed into proteins. One way gene expression is regulated is by pausing “transcription” — the process by which RNA is synthesized from its DNA template by an enzyme called RNA polymerase. Now, researchers have worked out the mechanism of transcription pausing in some bacteria using cryo-electron microscopy (cryo-EM), which allows them to determine to atomic scale the structures of the RNA polymerase before, during, and just after a pause of RNA production. Elucidating the mechanism of pausing transcription is crucial to understanding basic cellular function.

One of the key components of transcription pausing in the bacteria is a protein factor called NusG, which is conserved across organisms, including humans, such that the pausing mechanism revealed by this study may be broadly applicable for understanding gene regulation in all organisms on Earth. The insight could also be used to identify new anti-bacterial agents that target and inhibit transcription pausing thus disrupting proper gene expression and cellular function.

Creating 3D objects with sound

The use of sound waves to create a pressure field to print particles. 
Image Credit: © MPI for Medical Research, Heidelberg University/ Kai Melde

Creating 3D objects with sound

Scientists from the Max Planck Institute for Medical Research and the Heidelberg University have created a new technology to assemble matter in 3D. Their concept uses multiple acoustic holograms to generate pressure fields with which solid particles, gel beads and even biological cells can be printed. These results pave the way for novel 3D cell culture techniques with applications in biomedical engineering.

Additive manufacturing or 3D printing enables the fabrication of complex parts from functional or biological materials. Conventional 3D printing can be a slow process, where objects are constructed one line or one layer at a time. Researchers in Heidelberg and Tübingen now demonstrate how to form a 3D object from smaller building blocks in just a single step. “We were able to assemble microparticles into a three-dimensional object within a single shot using shaped ultrasound”, says Kai Melde, postdoc in the group and first author of the study. “This can be very useful for bioprinting. The cells used there are particularly sensitive to the environment during the process”, adds Peer Fischer, Professor at Heidelberg University.

Yellow evolution: Unique genes led to new species of monkeyflower

 Plants of the genus Mimulus (Monkeyflowers) have a great diversity of flower color and shape.
Photo Credit: Yuan Mimulus Lab, Pete Morenus | UConn

Monkeyflowers glow in a rich assortment of colors, from yellow to pink to deep red-orange. But about 5 million years ago, some of them lost their yellow. In the Feb. 10 issue of Science, UConn botanists explain what happened genetically to jettison the yellow pigment, and the implications for the evolution of species.

Monkeyflowers are famous for growing in harsh, mineral-rich soils where other plants can’t. They are also famously diverse in shape and color. And monkeyflowers provide a textbook example of how a single-gene change can make a new species. In this case, a monkeyflower species lost the yellow pigments in the petals but gained pink about 5 million years ago, attracting bees for pollination. Later, a descendent species accumulated mutations in a gene called YUP that recovered the yellow pigments and led to production of red flowers. The species stopped attracting bees. Instead, hummingbirds pollinated it, isolating the red flowers genetically and creating a new species.

UConn botanist Yaowu Yuan and postdoctoral researcher Mei Liang (currently a professor at South China Agricultural University), with collaborators from four other institutes, have now shown exactly which gene it is that changed to prevent monkeyflowers from making yellow. Their research, published this week in Science, adds weight to a theory that new genes create phenotypic diversity and even new species.

Mosquito’s DNA could provide clues on gene expression, regulation

Vinícius Contessoto (left) and José Onuchic are lead co-authors on the study published last month in Nature Communications.
Vinícius Contessoto
 is a researcher in the Center for Biological Theoretical Physics at Rice University.
José Onuchic
 is the Harry C. and Olga K. Wiess Chair of Physics and professor of chemistry and biosciences at Rice University.
Photo Credit: Gustavo Raskosky/Rice University

When it comes to DNA, one pesky mosquito turns out to be a rebel among species.

Researchers at Rice University’s Center for Theoretical Biological Physics (CTBP) are among the pioneers of a new approach to studying DNA. Instead of focusing on chromosomes as linear sequences of genetic code, they’re looking for clues on how their folded 3D shapes might determine gene expression and regulation.

For most living things, their threadlike chromosomes fold to fit inside the nuclei of cells in one of two ways. But the chromosomes of the Aedes aegypti mosquito — which is responsible for the transmission of tropical diseases such as dengue, chikungunya, zika, mayaro and yellow fever — defy this dichotomy, taking researchers at the CTBP by surprise.

The Aedes aegypti’s chromosomes organize as fluid-yet-oriented “liquid crystals,” different from all other species, according to their study published in Nature Communications.

How protein-rich droplets form

Martina Havenith-Newen has gained new insights by combining two methods.
Photo Credit: © RUB, Marquard

Terahertz spectroscopy can be used to explain the spontaneous formation of protein-rich droplets, which may lead to neurodegenerative diseases.

With the help of a new method, terahertz calometry, it is a research team of the Bochum Cluster of Excellence Ruhr Explores Solvation RESOLV succeeded in re-examining the spontaneous phase separation into a protein-rich and a low-protein phase in one solution. It is believed that the protein-rich droplets favor the formation of neurotoxic protein aggregates - a starting point for neurodegenerative diseases. The researchers around Prof. Dr. Martina Havenith, holder of the Chair for Physical Chemistry II at the Ruhr University Bochum, reports in the Journal of Physical Chemistry Letters from 6. February 2023.

Molecular level and time resolution in the picosecond range

The study is based on the work in the Terahertz-Calorimetry project, which was funded by the European Research Council with an Advanced Grant. "The visionary idea in the project was to marry two powerful techniques in physical chemistry - laser spectroscopy and calorimetry -" explains Grantee Martina Havenith.

Chemists Optimized Ceramic Material for Hydrogen Energy

The Institute of Hydrogen Energy is creating materials and technologies.
Photo Credit: Anna Popova

The team of scientists from the Institute of High-Temperature Electrochemistry, Ural Branch of the Russian Academy of Sciences, and the Ural Federal University has obtained a ceramic material for hydrogen energy. Chemists managed to synthesize, study, and improve the properties of layered barium stannate. This material can be used in fuel cells and electrolyzers. They are used to produce hydrogen or electrical energy. The scientists described the synthesis process and chemical properties of the material in an article in the Journal of Alloys and Compounds. 

"We have been investigating barium stannate, an understudied layered material, for use in high-temperature devices. We prepared samples and found that it begins to partially decompose into oxides when stored outdoors for long periods of time. We were able to improve the stability by adding lanthanum, but we did not completely eliminate the problem. However, since the material as a whole has quite good electron-conducting properties, it can certainly be used for applications as long as its contact with air is excluded. For example, lithium-containing components in lithium-ion batteries are also used in isolation because they ignite in contact with air," explains study co-author Dmitry Medvedev, head of the Hydrogen Energy Laboratory at the Ural Federal University.

Disrupted flow of brain fluid may underlie neurodevelopmental disorders

The addition of a magenta tracer molecule illustrates the flow of fluid around the brain, revealing that neurons in the hippocampus (cyan), the brain’s memory center, are awash in fluid. Researchers at Washington University School of Medicine in St. Louis have discovered that this fluid flows to areas critical for normal brain development and function, suggesting that disruptions to its circulation may play an underrecognized role in neurodevelopmental disorders.
Photo Credit: Shelei Pan and Peter Yang/School of Medicine

The brain floats in a sea of fluid that cushions it against injury, supplies it with nutrients and carries away waste. Disruptions to the normal ebb and flow of the fluid have been linked to neurological conditions including Alzheimer’s disease and hydrocephalus, a disorder involving excess fluid around the brain.

Researchers at Washington University School of Medicine in St. Louis created a new technique for tracking circulation patterns of fluid through the brain and discovered, in rodents, that it flows to areas critical for normal brain development and function. Further, the scientists found that circulation appears abnormal in young rats with hydrocephalus, a condition associated with cognitive deficits in children.

The findings, available online in Nature Communications, suggest that the fluid that bathes the brain — known as cerebrospinal fluid — may play an underrecognized role in normal brain development and neurodevelopmental disorders.